1dqs
From Proteopedia
(New page: 200px<br /><applet load="1dqs" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dqs, resolution 1.8Å" /> '''CRYSTAL STRUCTURE OF ...) |
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| - | [[Image:1dqs.gif|left|200px]]<br /><applet load="1dqs" size=" | + | [[Image:1dqs.gif|left|200px]]<br /><applet load="1dqs" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1dqs, resolution 1.8Å" /> | caption="1dqs, resolution 1.8Å" /> | ||
'''CRYSTAL STRUCTURE OF DEHYDROQUINATE SYNTHASE (DHQS) COMPLEXED WITH CARBAPHOSPHONATE, NAD+ AND ZN2+'''<br /> | '''CRYSTAL STRUCTURE OF DEHYDROQUINATE SYNTHASE (DHQS) COMPLEXED WITH CARBAPHOSPHONATE, NAD+ AND ZN2+'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Dehydroquinate synthase (DHQS) has long been regarded as a catalytic | + | Dehydroquinate synthase (DHQS) has long been regarded as a catalytic marvel because of its ability to perform several consecutive chemical reactions in one active site. There has been considerable debate as to whether DHQS is actively involved in all these steps, or whether several steps occur spontaneously, making DHQS a spectator in its own mechanism. DHQS performs the second step in the shikimate pathway, which is required for the synthesis of aromatic compounds in bacteria, microbial eukaryotes and plants. This enzyme is a potential target for new antifungal and antibacterial drugs as the shikimate pathway is absent from mammals and DHQS is required for pathogen virulence. Here we report the crystal structure of DHQS, which has several unexpected features, including a previously unobserved mode for NAD+-binding and an active-site organization that is surprisingly similar to that of alcohol dehydrogenase, in a new protein fold. The structure reveals interactions between the active site and a substrate-analogue inhibitor, which indicate how DHQS can perform multistep catalysis without the formation of unwanted by-products. |
==About this Structure== | ==About this Structure== | ||
| - | 1DQS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Emericella_nidulans Emericella nidulans] with ZN, CL, NAD and CRB as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-dehydroquinate_synthase 3-dehydroquinate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.3.4 4.2.3.4] Full crystallographic information is available from [http:// | + | 1DQS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Emericella_nidulans Emericella nidulans] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=NAD:'>NAD</scene> and <scene name='pdbligand=CRB:'>CRB</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/3-dehydroquinate_synthase 3-dehydroquinate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.3.4 4.2.3.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DQS OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Emericella nidulans]] | [[Category: Emericella nidulans]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Brown, K | + | [[Category: Brown, K A.]] |
| - | [[Category: Carpenter, E | + | [[Category: Carpenter, E P.]] |
| - | [[Category: Frost, J | + | [[Category: Frost, J W.]] |
| - | [[Category: Hawkins, A | + | [[Category: Hawkins, A R.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: CRB]] | [[Category: CRB]] | ||
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[[Category: zn2+ binding]] | [[Category: zn2+ binding]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:19:26 2008'' |
Revision as of 10:19, 21 February 2008
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CRYSTAL STRUCTURE OF DEHYDROQUINATE SYNTHASE (DHQS) COMPLEXED WITH CARBAPHOSPHONATE, NAD+ AND ZN2+
Overview
Dehydroquinate synthase (DHQS) has long been regarded as a catalytic marvel because of its ability to perform several consecutive chemical reactions in one active site. There has been considerable debate as to whether DHQS is actively involved in all these steps, or whether several steps occur spontaneously, making DHQS a spectator in its own mechanism. DHQS performs the second step in the shikimate pathway, which is required for the synthesis of aromatic compounds in bacteria, microbial eukaryotes and plants. This enzyme is a potential target for new antifungal and antibacterial drugs as the shikimate pathway is absent from mammals and DHQS is required for pathogen virulence. Here we report the crystal structure of DHQS, which has several unexpected features, including a previously unobserved mode for NAD+-binding and an active-site organization that is surprisingly similar to that of alcohol dehydrogenase, in a new protein fold. The structure reveals interactions between the active site and a substrate-analogue inhibitor, which indicate how DHQS can perform multistep catalysis without the formation of unwanted by-products.
About this Structure
1DQS is a Single protein structure of sequence from Emericella nidulans with , , and as ligands. Active as 3-dehydroquinate synthase, with EC number 4.2.3.4 Full crystallographic information is available from OCA.
Reference
Structure of dehydroquinate synthase reveals an active site capable of multistep catalysis., Carpenter EP, Hawkins AR, Frost JW, Brown KA, Nature. 1998 Jul 16;394(6690):299-302. PMID:9685163
Page seeded by OCA on Thu Feb 21 12:19:26 2008
Categories: 3-dehydroquinate synthase | Emericella nidulans | Single protein | Brown, K A. | Carpenter, E P. | Frost, J W. | Hawkins, A R. | CL | CRB | NAD | ZN | Aromatic amino acid biosynthesis | Cyclase | Intra molecular aldol condensation | Lyase | Multi-step enzyme | Nad+ binding | Oxidoreductase | Phosphate elimination | Shikimate pathway enzyme | Zn2+ binding
